Review of the UK NEQAS (H) digital morphology pilot scheme for continuing professional development accessed via the internet.

UK NEQAS (H) developed and instigated a pilot scheme for digital morphology, which was accessed by participants over the internet in order to assess the viability of using high quality images as an educational tool for continuing professional development. The pilot scheme was trialled over a 2-year period with eight releases totalling 16 morphology cases. Digital images allowed participating individuals to examine and comment on exactly the same cells and compare their findings with those of other participants, consensus data from traditional glass slide surveys and expert opinion. Feedback from participants on their experience was then relayed back to the development team by UK NEQAS (H) in order to drive the educational format and to ensure that any new scheme would meet the requirements of the users.

The use of digital 'virtual slides' in the quality assessment of haematological morphology: results of a pilot exercise involving UK NEQAS(H) participants.

We report the results of a pilot study assessing the use of digital 'virtual slides' in haematological quality assessment. Conducted together with the UK National External Quality Assessment Scheme for General Haematology, the study involved 166 separate participants, using the format of a typical assessment exercise. The results revealed substantial concordance of observations made using digital slides with those reported in previous glass slide surveys that used identical cases. Participant feedback strongly supported the use of electronic slides in teaching and assessment roles. Our results suggest roles for this new electronic resource in external quality assessment (EQA), education and continuing professional development.

Misclassification of suicide-the contribution of opiates.

The reliability of suicide reporting remains a concern. Problems include procedural deficiencies, ambiguous evidence and the determination of intent. In this study, Queensland Suicide Register (QSR) data were compared to the usual official source - the Australian Bureau of Statistics (ABS). QSR deaths were coded as beyond reasonable doubt, probable and possible. These categories were analysed by methods and demographic variables to determine the nature of difficult-to-classify suicides. QSR suicides exceeded ABS especially for females, ages 25-44, and the methods overdose, drowning and 'other methods'. Opiate overdoses were most difficult to code. Ambiguous circumstantial information and unclear intent were major impediments. Nations witnessing rising rates of deaths due to drug abuse need to monitor undetermined and accidental deaths as well as suicides.

Suicides in an Australian inpatient environment.

Associated stressful life events both within and outside the hospital environment may contribute to the high-risk environment. The cohort studied here was hospitalized for a significant psychiatric problem, a factor which puts them in the high-risk category. When the severe psychiatric diagnosis is combined with a significant stressful life event, the risk of suicide is increased significantly.

Design and synthesis of thiol containing inhibitors of matrix metalloproteinases.

A series of thiol containing derivatives was prepared. Several of these compounds were found to inhibit matrix metalloproteinases 1, 3, and 9 with selectivity towards 3 and 9. Compounds 15, 20, and 22 were administered to rats orally at 75 mumol/kg. Drug levels of compounds 20 and 22 in the plasma were found to exceed the IC50 values for MMP 3 and 9 four hours after administration.

Involvement of alcohol in murder suicides.

The blood alcohol levels present post mortem for all murder-suicides identified via the Queensland Suicide Register were compared with those of a sample of suicides matched on age, sex and method. No differences in the levels of alcohol were found.

Mercaptoacyl dipeptides as orally active dual inhibitors of angiotensin-converting enzyme and neutral endopeptidase.

Dual inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP, EC 3.4.24.11) and angiotensin-I-converting enzyme (ACE, EC 2.4.15.1), have been the focus of much clinical interest for the treatment of hypertension and congestive heart failure. We have previously reported that compound 2 (N-[[1-[(2(S)-mercapto-3-methyl-1-oxobutyl) amino]-1-cyclopentyl]-carbonyl]-L-tyrosine) was a potent dual inhibitor in vitro (IC50 (ACE) = 7.0 nM, IC50 (NEP) = 1.5 nM) (Fink et al. J. Med. Chem. 1995, 38, 5023-5030). This compound was found to have oral activity; however, its duration of effect was short. A series of thioacetate carboxylic acid ester analogs of compound 2 was prepared. Modifications were also made to the tyrosine phenol. These compounds were evaluated for their ability to inhibit plasma ACE activity when administered orally to conscious normotensive rats. Most of the compounds prepared were found to be orally active with longer durations of effect than compound 2. Compound 38 (N-[[1-[(2(S)-(acetylthio)-3-methyl-1-oxobutyl) amino]-1-cyclopentyl]carbonyl]-O-methyl-L-tyrosine ethyl ester), administered at 11.7 mg/kg po, was found to be more efficacious than captopril at 10 mg/kg po. This compound was also found to inhibit plasma NEP activity following oral administration to conscious rats and was more efficacious than acetorphan. Compound 38 was found to lower blood pressure in the aorta-ligated rat and the spontaneously hypertensive rat when administered orally. The synthesis and biological activity of these dual inhibitors are discussed.